The objective of the proposed research is to identify and further characterize the biochemical and physiologic pathways that are responsible for the inflammation associated with urticaria, angioedema, late phase cutaneous reactions, and atopic and contact dermatitis. We will also characterize the immune response and inflammatory mechanisms of Lyme disease. We will determine the mechanism of bradykinin degradation in human plasma, develop assays for the degradation products, and purify and characterize the responsible enzymes. We will also purify and characterize histamine releasing factors (HRF) derived from human mononuclear cells. We will do c-DNA and/or genomic cloning of the factor(s) and therefore determine its amino acid sequence. We will develop functional and immunologic assays for HRF and apply them to the aforementioned disorders. We will also continue studies of mediator release in vitro and in vivo in various types of physically induced hives, hereditary and non-hereditary angioedema, and chronic urticaria. Emphasis will be placed on definitively identifying and type of kinin responsible for the swelling of hereditary angioedema, and the possible role of HRF in late phase cutaneous reactions, contact dermatitis, atopic dermatitis, and chronic urticaria. Finally, we will continue studies of Lyme disease, a common endemic disorder on Long Island and identify the antigens to which immune responses are directed, determine the nature of the immune response, and the mediator pathways responsible for tissue inflammation.